Improving extent of glioblastoma resection by combining volumetric MRSI and 5-ALA

描述（由申请人提供）：胶质母细胞瘤（GBM）是最常见的原发性脑肿瘤，几乎都是致命的。GBM患者的标准治疗是神经外科切除术，然后进行放射治疗和替莫唑胺化疗。传统的GBM神经外科切除术依赖于使用基于术前对比增强MRI的神经导航;然而，已知非增强、浸润性肿瘤远超出增强边缘。GBM肿瘤很少转移到中枢神经系统（CNS）之外。大多数肿瘤会在最初肿瘤的几厘米内复发，使疾病的局部控制成为高度优先事项。然而，GBM肿瘤的根治性切除是具有挑战性的，因为它们在相邻正常脑内具有浸润性。目前的技术依赖于显微外科手术、基于对比增强MRI的神经导航以及术中MRI的使用，以最大限度地实现手术切除。鉴于肿瘤浸润和复发的模式，更完整的切除这些肿瘤可能会改善局部控制，并最终提高患者的生存率。我们建议通过结合磁共振波谱成像（MRSI）和5-氨基乙酰丙酸（5-ALA）荧光引导手术（FGS），提高GBM切除范围超出MRI对比增强肿瘤边缘的患者。通过使用这两种技术，GBM患者可以接受更完整的肿瘤切除术。MRSI提供了肿瘤组织内内源性代谢物的分子图像/图谱，可用于区分肿瘤和非肿瘤病变。胆碱/NAA比值图可以清楚地显示浸润性，高级别肿瘤超出MRI对比度增强区发现术前MRI。另一方面，5- ALA FGS提供术中实时指导以区分肿瘤与正常周围脑组织。通过将MRI神经导航配准的MRSI与5-ALA FGS结合，神经外科医生将能够将非功能性肿瘤患者的肿瘤切除边缘推到对比增强边界之外。我们的建议将利用MRSI技术和图像配准和可视化工具的最新进展，这将允许临床医生更容易地显示，审查和解释MRSI数据，从而使常规临床应用成为可能。MRSI和FGS的使用可能有助于更安全地切除增强肿瘤边缘以外的肿瘤组织，可能改善GBM患者的总体生存临床结局。

DESCRIPTION (provided by applicant): Glioblastoma (GBM) is the most common primary brain tumor and is almost uniformly fatal. The standard of care for GBM patients is neurosurgical resection, followed by radiation therapy and temozolomide chemotherapy. Traditional neurosurgical resection of GBMs has relied on the use of neuronavigation based on pre-operative contrast-enhanced MRI; however, it is known that nonenhancing, infiltrating tumor extends well beyond the margins of enhancement. GBM tumors rarely metastasize outside the central nervous system (CNS). Most tumors will recur within centimeters of the initial tumor, making local control of disease a high priority. Radical resection of GBM tumors, however, is challenging due to their infiltrative nature within the adjacent normal brain. Current technology relies on microsurgery, neuronavigation based on contrast- enhanced MRI, and the use of intraoperative MRI when available to maximize surgical resection. Given the patterns of tumor infiltration and recurrence, more complete resection of these tumors may improve local control and, ultimately, patient survival. We propose to improve the extent of GBM resection beyond the MRI contrast-enhancing tumor margins in patients by combining magnetic resonance spectroscopic imaging (MRSI) and 5-aminolevulinic acid (5-ALA) fluorescent-guided surgery (FGS). With the use of both of these technologies, GBM patients may undergo more complete resections of their tumor. MRSI provides, which can display the distribution of endogenous metabolites within tumor tissue as a molecular image/map, has shown benefit for the differentiation of tumor and non-tumor lesions. Choline/NAA ratio maps derived from these studies can clearly demonstrate infiltrative, high grade tumor beyond MRI contrast-enhancing regions found on preoperative MRI. On the other hand, 5- ALA FGS provides intraoperative real-time guidance to differentiate tumor from normal surrounding brain tissue. By including MRSI registered with MRI neuronavigation in combination with 5-ALA FGS, neurosurgeons will be able to push the margin of tumor resection outside the boundary of contrast-enhancement in patients with noneloquent tumors. Our proposal will take advantage of recent advances in MRSI technology and the image registration and visualization tools, which will permit clinicians to display, review and interpret MRSI data more easily, thereby making routine clinical application possible. Use of MRSI and FGS may facilitate more safe removal of tumor tissue beyond the enhancing tumor margin, potentially improving overall survival clinical outcomes for patients with GBM.